Rat embryo exposure to all-trans retinoic acid results in long-term cognitive deficits

The present study examines in particular associative learning and aversive memory abilities in adult Sprague Dawley rats exposed to all-trans retinoic acid (ATRA) in the period spanning gestational days (GD) 11-13. The ATRA dosage of 2.5 mg/kg compatible with high neonatal survival, sufficient to supply offspring for later behavioral testing, was used. The results show that the GD 11-13 ATRA exposure compromises the ability of rats to learn an active avoidance task. Indeed, unlike control rats, the ATRA-treated rats did not improve in performance over blocks of training, the number of attempts they made to avoid foot shock being significantly affected. The memory ability, assessed with the passive avoidance paradigm, was not affected by ATRA exposure. The results provide further evidence that, beyond gross CNS malformations, gestational ATRA exposure induces long-term cognitive deficits in the offspring, thus raising further warning for better control of retinoid safety during pregnancy, an aspect relevant to human health protection within the regulatory environment.